Cofilin mediates tight-junction opening by redistributing actin and tight-junction proteins.
We previously found that capsaicin induces tight-junction (TJ) opening accompanied with cofilin dephosphorylation/activation in intestinal Caco-2 cells. Here, we examined the role of cofilin in TJ regulation, and analyzed the structural events that lead to TJ opening. We transfected Caco-2 cells with wild-type cofilin [cofilin(wt)] or its constitutively active mutant cofilin(S3A). We found that the decreases in transepithelial electrical resistance (TER) was slower in cofilin(wt) transfectants and faster in cofilin(S3A) mutants than in vector controls. Moreover, cofilin dephosphorylation corresponded to the rate of TER decrease. Capsaicin treatment changed the localization of TJ proteins and altered the F-actin structure, but in a manner different from those depend on myosin light chain kinase (MLCK). These results strongly support the importance of cofilin in TJ opening, suggesting cofilin as a target for TJ permeability regulation in epithelial cells.
Nagumo
Yoko
Y
Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan. nag@agbi.tsukuba.ac.jp
Han
Junkyu
J
Bellila
Amor
A
Isoda
Hiroko
H
Tanaka
Toshiyuki
T
D000199:Actins / Q000378:metabolism*; D018938:Caco-2 Cells; D002211:Capsaicin / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D062445:Claudin-1; D051338:Cofilin 1 / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein
D000199:Actins; C568108:CLDN1 protein, human; D062445:Claudin-1; D051338:Cofilin 1; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D009218:Myosins; D002211:Capsaicin